There is a growing need for new concepts in surgical wound closure due to limitations associated with invasive surgical closure techniques such as sutures and staples.[1-3] Medical adhesives and sealants that form in situ, many of which are approved for human clinical use, offer less invasive alternatives to conventional surgical closure techniques.[4-6] Several medical sealants are based on native proteins, for example fibrin glue and chemically cross-linked albumin.[4-7] While protein-based gels currently enjoy widespread use, their limitations include the possibility for disease transmission, allergic reactions, and poor mechanical properties.[6,8,9] As a result of these shortcomings, several synthetic surgical adhesives have been developed, including cyanoacrylates and hydrogels based on polymers such as poly(ethylene oxide) (PEO).[10-20] Cyanoacrylates exhibit excellent mechanical performance but their widespread use for internal procedures is limited by toxicity concerns.[10-12]PEO-based hydrogels, such as FocalSeal®, CoSeal®, and DuraSeal®, have satisfactory mechanical performance, are non-immunogenic, and have been used in cardiovascular,[13,14] pulmonary,[15,16] and dural[17,18] surgical procedures, among others.[19,20]
Swelling due to water absorption is a general feature of chemically cross-linked hydrophilic polymer networks.[21] The equilibrium swelling behavior of a polymer hydrogel is a reflection of the polymer-solvent interaction parameter, polymer architecture, extent of cross-linking, and polymer volume fraction.[22] In the context of in-situ forming medical adhesives, rapid covalent cross-linking of an aqueous polymer solution generally yields polymer hydrogels that are prone to significant swelling upon immersion into excess water.[2 24] For PEO-based medical adhesives, observed swelling values range from 30% to >700%.[23,25,26] The consequences of swelling on the mechanical performance of tissue adhesives are underappreciated in the literature, as standard adhesion test methods often probe adhesion strength under non-equilibrium swelling conditions.[27] Swelling of medical adhesives and sealants in the minutes and hours following deployment in vivo can lead to severe medical complications such as local nerve compression.[28-30]
One possible approach to preventing swelling of polymer hydrogel tissue adhesives is to employ thermosensitive polymers.[31-35] Block copolymers of PPO and PEO, including commercially available multi-arm block copolymers composed of central PPO blocks and peripheral PEO blocks (Tetronic®), exhibit interesting thermosensitive behavior due to the hydrophilic-to-hydrophobic transition of the PPO block that occurs by mild warming.[31-34] Previous reports of chemically cross-linked Tetronic® hydrogels for cell encapsulation and tissue adhesion have appeared in the literature,[31,36-44] though systematic studies of the relationship between chemical cross-linking, thermal transition, and mechanical properties in the context of medical adhesion have not been undertaken.